Methods and compositions for the repair and/or regeneration of damaged myocardium

Abstract

Methods, compositions, and kits for repairing damaged myocardium and/or myocardial cells including the administration cytokines are disclosed and claimed.

1. A method for restoring functional and structural integrity to damaged myocardium in a subject in need thereof, the method comprising administering to the subject an effective amount of a cytokine to form a chemotactic gradient in the subject's heart sufficient to cause adult cardiac stem cells resident in the heart to migrate to the area of the damaged myocardium, wherein said gradient is formed by multiple injections of said cytokine from storage areas of said resident adult cardiac stem cells to a border zone of the damaged myocardium, and wherein the functional and structural integrity of the damaged myocardium is restored following the migration of adult cardiac stem cells to the area of damaged myocardium. 
     
     
       2. A method for restoring functional and structural integrity to damaged myocardium in a subject in need thereof, the method comprising administering to the subject an effective amount of at least one isolated cytokine to form a chemotactic gradient in the subject's heart sufficient to cause adult cardiac stem cells resident in the heart to replicate and migrate to the area of the damaged myocardium, wherein said gradient is formed by multiple injections of said at least one cytokine from storage areas of said resident adult cardiac stem cells to a border zone of the damaged myocardium, and wherein the functional and structural integrity of the damaged myocardium is restored following the migration of adult cardiac stem cells to the area of damaged myocardium. 
     
     
       3. The method of  claim 2 , wherein said stem cells are c-kit POS . 
     
     
       4. The method of  claim 2 , wherein the injections are intramyocardial. 
     
     
       5. The method of  claim 2 , wherein the injections are trans-epicardial. 
     
     
       6. The method of  claim 2 , wherein the multiple injections comprise variable concentrations of one or more of said cytokines. 
     
     
       7. The method of  claim 2 , wherein the adult cardiac stem cells differentiate into myocytes, smooth muscle cells, and endothelial cells. 
     
     
       8. The method of  claim 7  wherein at least some of the differentiated adult cardiac stem cells assemble into myocardial tissue and myocardial vessels. 
     
     
       9. The method of  claim 2 , wherein said method also regenerates cardiac vessels. 
     
     
       10. The method of  claim 2 , wherein the storage areas of said resident adult cardiac stem cells are one or more of the subject's myocardial apex, left atrium, and right atrium. 
     
     
       11. The method of  claim 2 , wherein at least two of the injections are done at opposite sides of the border zone. 
     
     
       12. The method of  claim 2 , wherein the at least one cytokine is capable of mobilizing adult stem cells in vitro. 
     
     
       13. The method of  claim 12 , wherein the at least one cytokine is selected from the group consisting of hepatocyte growth factor, stem cell factor, and granulocyte monocyte colony stimulating factor. 
     
     
       14. The method of  claim 13 , wherein the at least one cytokine is hepatocyte growth factor. 
     
     
       15. The method of  claim 14 , wherein said hepatocyte growth factor is administered at varying concentrations of between 0 and 400 ng/ml at different places of administration. 
     
     
       16. The method of  claim 15 , wherein the varying concentrations of the hepatocyte growth factor increase progressively in a direction towards the damaged myocardium. 
     
     
       17. The method of  claim 14  wherein said hepatocyte growth factor is administered at varying concentrations of between 50 and 200 ng/ml at different places of administration. 
     
     
       18. The method of  claim 2 , further comprising administering a second cytokine, wherein the second cytokine induces proliferation of adult cardiac stem cells. 
     
     
       19. The method of  claim 18 , wherein the second cytokine is insulin-like growth factor-1. 
     
     
       20. The method of  claim 19 , wherein said insulin-like growth factor-1 is administered at a concentration less than 500 ng/ml. 
     
     
       21. The method of  claim 19 , wherein said insulin-like growth factor-1 is administered at a concentration of between 150 and 250 ng/ml. 
     
     
       22. The method of  claim 19 , wherein said insulin-like growth factor-1 is administered at a concentration of 200 ng/ml.